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MUTATIONAL AND TRANSCRIPTIONAL RESPONSES OF STATIONARY- AND LOGARITHMIC-PHASE SALMONELLA TO MX: CORRELATION OF MUTATIONAL RESPONSE TO CHANGES IN GENE EXPRESSION
Citation:
WARD, W. O., C. SWARTZ, S. PORWOLLIK, N. M. HANLEY, S. H. WARREN, M. MCCLELLAND, AND D. M. DEMARINI. MUTATIONAL AND TRANSCRIPTIONAL RESPONSES OF STATIONARY- AND LOGARITHMIC-PHASE SALMONELLA TO MX: CORRELATION OF MUTATIONAL RESPONSE TO CHANGES IN GENE EXPRESSION. Presented at The 9th International Conference on Environmental Mutagens, and the 36th Annual Meeting of the Environmental Mutagen Society, San Francisco, CA, September 03 - 08, 2005.
Description:
We measured the mutational and transcriptional response of stationary-phase and logarithmic-phase S. typhimurium TA100 to 3 concentrations of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). The mutagenicity of MX in strain TA100 was evaluated in a 30-min suspension assay. MX induced approximately two times higher mutant yields (rev/�-M) in stationary-phase cells relative to log-phase cells. However, the highest concentration of MX induced gene expression changes in both logarithmic-phase cells and stationary-phase cells. Among the 21 genes that were upregulated in both of these phases, twelve were mediators of the SOS response. Consistent with the activation of the SOS response, a major pathway for spontaneous induction of prophage excision, is the up-regulation of 13 Fels-1 and 8 Gifsy-2 prophage genes in log phase. Also consistent with the response to MX-induced DNA damage, log-phase cells showed up-regulation of DNA repair genes with a possible slight repression of the replicative DNA polymerase III. In addition to these transcriptional responses to DNA damage, a comprehensive analysis of the 143 KEGG pathways defined in S. typhimurium identified altered expression of sulfur metabolism genes and a down-regulation of flagellar assembly and the Type III secretion system genes. These transcriptional changes suggest that MX interferes with cellular metabolism through mechanisms other than DNA damage. To determine if these global transcriptional changes are representative of MX, we plan to examine global gene expression in TA100 treated with MX congeners.